The impairment of cardiac performance appears to be a common denominator in many forms of circulatory shock both in humans and experimental animals. Attempts to alter cardiac performance in shock by the use of commonly employed intropic agents (i.e., digitalis glycosides, glucagon, isoproterenol, etc.) has not met with much success. We have correlated the observed decreases in cardiac capacity with the production and plasma accumulation of a myocardial depressant factor (MDF). This cardiotoxic peptide originates from the ischemic pancreas during shock and its formation appears to result from the release of lysosomal proteases. Since measures which enhance the removal of MDF from the systemic circulation (hemodialysis), prevent its production (pancreatectomy, protease inhibitor therapy), or alter the response of pancreatic lysosomes to ischemia (chronic pancreatic duct ligation) significantly improve survival in experimental shock, agents which act at the subcellular level to maintain lysosomal integrity should be of benefit in the therapy of circulatory shock. Our preliminary studies indicate that 'pharmacologic' doses of glucocorticoids and prostaglandins may bestow a significant degree of protection in shock. The present study will attempt to evaluate the protective action of methylprednisolone and prostaglandins A1, E1, E2, and F2 in the intact animal in several forms of circulatory shock. In addition, the action of these agents will be studied in the isolated perfused pancreas and in vitro using lysosomal suspensions under conditions (i.e., acidosis, ischemia, and/or hypoxia) normally found in the intact shocked animal. Thus, we can thoroughly evaluate the capacity of these pharmacologic agents to modify the hemodynamic, biochemical and ultrastructural sequelae of circulatory shock and further reveal the relative importance and interrelationships between each of these sequelae in the total picture of circulatory shock.